Expression of synaptic cell adhesion molecules, such as neuroligin, neurexin and SynCAM, in nonneural cells can induce pre- or postsynaptic differentiation in contacting neurites of cocultured neurons [1-3]. We used this assay to demonstrate that NGL, a family of cell adhesion molecules that associates with the netrin-G family of cell adhesion molecules and the postsynaptic scaffolding protein PSD-95, can induce presynaptic differentiation in contacting axons of cocultured neurons. Presynaptic differentiation was visualized by immunostaining for the presynaptic marker synapsin I. In addition, functional presynaptic differentiation was demonstrated by vesicle turnover experiments, which monitor the uptake of synaptotagmin luminal domain antibodies [4].